Link to depression and brain changes — Part 2

Neurotransmitters in adult neurogenesis

Several neurotransmitter systems may regulate adult CNS neurogenesis. Monoamine neurotransmitters are known to influence multiple aspects of neural development, including precursor proliferation, cell survival, axonal growth and synapse formation (29). The neurotransmitter systems covered here encompass the ‘traditional’ neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate, and neuromodulatory transmitters or neuromodulators such as dopamine, serotonin, and acetylcholine that are secreted by a small group of neurons and can affect neuronal activity through large brain areas. It is often suggested that the delayed therapeutic response for antidepressants could be due to their effects on neurogenesis. Such as, although SSRIs increase serotonin levels hours after drug administration if their administration leads to beneficial impacts, it usually takes 2–4 weeks of daily administration for those effects to appear. One would assume that if serotonin levels were causally linked to depression, then soon after serotonin levels increased, the mood would begin to improve much more rapidly. (30)

neurotransmitters and neurogenesis
source: https://link.springer.com/article/10.1007/s00441-017-2668-y

GABA & Glutamate

Glutamate is the primary excitatory and GABA the main inhibitory neurotransmitter in the mammalian cortex. Changes in glutamate and GABA metabolism may play essential roles in the control of cortical excitability (31). Growing evidence suggests that the neurotransmitters GABA and glutamate have a significant role in setting the timing for survival, proliferation, migration, synapse formation and integration of newly formed neurons in established synaptic networks (32).

“Even modest chronic deficits in GABAergic transmission in GABAAR γ2+/− mice impair the survival of adult-born hippocampal neurons, an effect that may explain hippocampal volume reductions were seen in chronically depressed patients”(33)

“Experimental evidence has demonstrated that glutamate is an essential factor for neurogenesis, whereas another line of research postulates that excessive glutamatergic neurotransmission is associated with the pathogenesis of depression….Low glutamate levels activate adaptive stress responses that include proteins that protect neurons against more severe stress. Conversely, abnormally high levels of glutamate, resulting from increased release and/or decreased removal, cause neuronal atrophy and depression. The dysregulation of the glutamatergic transmission in depression could be undermined by several factors including a decreased inhibition (γ-aminobutyric acid or serotonin) or an increased excitation (primarily within the glutamatergic system).”(34)

“…an excitotoxic concentration of glutamate, which killed between 60–80% of granule cell neurons on day 8 in vitro, mediated its toxic effect via a time-dependent apoptotic pathway.”(35)

Dopamine

Dopamine controls multiple physiological functions in the brain and periphery by acting on its receptors D1, D2, D3, D4, and D5. Dopamine receptors are G protein-coupled receptors (also called seven-transmembrane receptors) involved in the regulation of motor activity and several neurological disorders such as Parkinson’s disease (PD), schizophrenia, bipolar disorder, Alzheimer’s disease, and attention-deficit/hyperactivity disorder (ADHD). Reduced dopamine content in the nigrostriatal pathway is associated with the development of PD, along with the degeneration of dopaminergic neurons in the substantia nigra region.

“Dopamine receptors are widely expressed in the hippocampal dentate gyrus and SVZ [subventricular zone] region and are actively involved in the modulation of neurogenesis in basal forebrain structures, thereby supporting the hypothesis that dopamine plays a role in neurogenesis and brain plasticity.”(36)

“On top of its role in motor control, mood and as a neurotransmitter, dopamine also plays a vital role in neuronal proliferation and differentiation in the adult CNS. The dopaminergic projections directly innervate the SVZ and hippocampus, thus directly influencing the microenvironment of these niches to regulate neural stem cells dynamics…suggested that chronic treatment with the D2-like antagonist, haloperidol, in adult rats led to an increase in the number of primary neurospheres obtained from the SVZ.”(37)

“Consistently, the numbers of proliferating cells in the subependymal zone and neural precursor cells in the subgranular zone and olfactory bulb are reduced in postmortem brains of individuals with Parkinson disease. These observations suggest that the generation of neural precursor cells is impaired in Parkinson disease as a consequence of dopaminergic denervation [loss of nerve supply].”(38)

Serotonin & Norepinephrine 

Serotonin or 5-hydroxytryptamine (5-HT) has a popular image as a contributor to feelings of well-being and happiness, though its actual biological function is complex and multifaceted, modulating cognition, reward, learning, memory, and numerous physiological processes such as gut function. In the human body, the majority of serotonin is made, stored, and released by cells in the gut lining. These cells make serotonin from the amino acid L-tryptophan. Norepinephrine (NE) also called Noradrenaline (NA), or Noradrenaline, is a neurotransmitter that functions in the human brain and body as both a hormone and neurotransmitter. In the brain, norepinephrine increases alertness and arousal, promotes vigilance, enhances the formation and retrieval of memory, and focuses attention. In the other parts of the body, norepinephrine increases heart rate and blood pressure, triggers the release of glucose from energy stores, increases blood flow to skeletal muscle, reduces blood flow to the gastrointestinal system, inhibits urination and slows the gut flow.

serotonin and norepinephrine
source: https://www.semanticscholar.org/paper/The-role-of-serotonin-in-adult-hippocampal-Alenina-Klempin/719283c5c651c2fd0d210e421f533cf9668bcd25

“Lesion of the 5-HT system is reported to decrease neurogenesis (Brezun and Daszula 2000), and preliminary studies demonstrate that administration of fenfluramine, which causes the release of 5-HT, increases adult neurogenesis in the hippocampus (Jacobs et al. 1998). In contrast, administration of a 5-HT1A antagonist, WAY 100,635, blocks fenfluramine-induction of neurogenesis, as well as the basal rate of neurogenesis in the absence of fenfluramine (Jacobs et al. 1998). These studies suggest that regulation of the 5-HT system and 5-HT1A receptors could contribute to the induction of adult neurogenesis by antidepressants, at least the effect of a 5-HT selective reuptake inhibitor.” (39)

“These results show that the effects of fluoxetine on LTP [long-term potentiation ] and behaviour both require neurogenesis and follow a similar delayed time course. The effects of chronic fluoxetine on the maturation and functional properties of young neurons may, therefore, be necessary for its anxiolytic/antidepressant activity and contribute to its delayed onset of therapeutic efficacy.”(40)

“Likewise, the lack of lesion effects upon progenitor survival or differentiation reported by Kulkarni et al. (2002), three weeks after BrdU [5-Bromo-2′-deoxyuridine (5-BrdU) is a thymidine analogue which is incorporated into DNA. 5-BrdU is routinely and extensively used to measure DNA synthesis and to label dividing cells. Consequently, 5-BrdU is used to study cell signalling and other processes that induce cell proliferation. Labelling was consistent with that detected here over a similar period. Thus, a noradrenergic control is likely to be exerted upon cellular and molecular factors that either directly or indirectly influence SGZ [subgranular zone ] progenitor proliferation, but not upon those influencing progenitor survival or differentiation.”(41)

“The dentate gyrus granule cell layer, whose neurons are generated following monoamine innervation, exhibited a 16.2% decrease in absolute neuron number. Thus in the absence of En2, developmental deficits in forebrain growth occur that correlate with reductions in norepinephrine levels and innervation.”(29)

Acetylcholine

Acetylcholine, Ach, is an ester of choline and acetic acid and is the most widely spread neurotransmitter. It is also the most plentiful neurotransmitter, which may be found in both the peripheral and central nervous systems. It was discovered by Henry Hallett Dale in the year 1914, and its existence was later confirmed by Otto Loewi. Acetylcholine works in various brain regions, for instance, basal ganglia, cortex, and hypothalamus and is required for memory and cognition, as well as motor control. The action of acetylcholine released at a synapse is ended through the breakdown of ACh by the enzyme acetylcholinesterase. (42)

“The cholinergic system also seems likely to regulate hippocampal neurogenesis in the adult brain, positively promoting proliferation, differentiation, integration and potentially survival of newborn neurons.”(43)

“We find that changes of forebrain ACh level primarily influenced the proliferation and/or the short-term survival as opposed to the long-term survival or differentiation of the new neurons. We further demonstrate that these newly born cells express the muscarinic receptor subtypes M1 and M4. Our data provide evidence that forebrain ACh promotes neurogenesis, and suggests that the impaired cholinergic function in AD may in part contribute to deficits in learning and memory through reductions in the formation of new hippocampal neurons.”(44)

Putting it all together

Now that we’ve established some of the factors involved in neurogenesis, it’s time to examine how we can leverage these inputs to optimise for neurogenesis and mitigate some of the assumed damage that is incurred due to long term stress and depression. To keep this post at readable length (already much longer than I expected) I won’t go into great depth on each item, but I’ll add plenty of references in that you can follow up yourself.

Optimising hormones for neurogenesis

The best way to begin optimising your hormones will be getting a full hormone blood panel performed. Dr Mark Gordon from http://www.tbimedlegal.com/ who specialises in treating traumatic brain injury via hormone modulation recommends getting these tested first;

Once you’ve had these tests done, you can start working with your primary care doctor (or an endocrinologist) to begin to address any irregularities. Some options could be; Testosterone replacement therapy (TRT)/Hormone replacement therapy (HRT), Clomiphene monotherapy, human chorionic gonadotropin (HCG), supplementing with; pregnenolone, DHEA, IGF-1, natural desiccated thyroid etc. It’s essential you work with a doctor due to the many feedback loops involved.

Optimising neurotrophic growth factors for neurogenesis

NGF
* Lion’s Mane Hericium erinaceus (45), (46), (47)
* PQQ Pyrroloquinoline quinone (48), (49)
* Noopept (50), (51), (52)
BDNF
* Exercise (53), (54)
* Lithium (55), (56), (57)
* Curcumin (58), (59), (60)
* Semax** (61), (62)
* NSI-189** (63)
GDNF
* NSI-189** (63)
* Selegiline* (64), (65), (66)
* Vitamin D (67), (68)
* Luteolin (69), (70 confounded by use of PEA as well and possible conflicts of interest)

(* = Prescription)
(**= Usually classed as a research chemical, as such long-term safety profile is undetermined)


Reducing neural inflammation
* Resveratrol (71), (72), (73)
* PEA N-Palmitoylethanolamine (74), (75), (76)
* CBD (77), (78), (79)
* Curcumin (80), (81)

Optimising neurotransmitter neurogenesis

Increasing neurotransmitters is the most common method for treating depression. It’s outside the scope of this article to go into detail on the variety of drugs that are used in this capacity. As such, I’ve limited this to a few over the counter methods, which are usually well tolerated and widely used as nootropics. If you want to do further research into prescription methods of modulation, I personally like these resources:

GABA/Glutamate
* Ashwagandha (82), (83)
* Lemon Balm (84), (85)
* NAC N-acetyl cysteine (86), (87)
* Sarcosine (88), (89)
Dopamine
* BPC157** (90), (91)
* SAM-e (92), (93)
Serotonin 
* Rhodiola Rosea (94)
* Bacopa (95), (96)
Norepinephrine
* Rhodiola Rosea (97)
Acetylcholine
* Alpha GPC (98), (99)
* ALCAR (100), (101)

Concluding remarks

To conclude this quite lengthy post, it appears that depression, particularly long bouts, can induce brain changes that may increase susceptibility to future mood disturbances. It may also be a case of the chicken and the egg where reduced growth factors produce a depressed state. I’d like to end on a note of caution though that the study of human neurogenesis is still in its infancy, let alone conclusively linking it to depression or influencing it. However, it’s an exciting new avenue of research, and many (if not all) of the methods mentioned also have corresponding research showing improvements in depressing in other studies whether that effect is achieved via neurogenesis or not.


FYI

I’m not a doctor etc. no medical body or the like has evaluated this information. Information is shared for educational purposes only and acquired through studying for myself. You should consult your primary care doctor before acting on any content, especially if you are taking medication, or have a medical condition/s.

P.S
Please let me know in the comments if you have any idea’s or suggestions on this post. Also, if you’ve found this post useful please consider sharing it and/or subscribing. I also have a twitter page where I share studies or posts I’ve found interesting on mental health issues.


References

1. Harvard Health Publishing. What causes depression? — Harvard Health [Internet]. Harvard Health. [cited 2018 Oct 30]. Available from: https://www.health.harvard.edu/mind-and-mood/what-causes-depression

2. Sapolsky RM. Depression, antidepressants, and the shrinking hippocampus. Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12320.

3. Paul Hamilton J, Siemer M, Gotlib IH. Amygdala volume in Major Depressive Disorder: A meta-analysis of magnetic resonance imaging studies. Mol Psychiatry. 2008 Nov;13(11):993.

4. Levy MJF, Boulle F, Steinbusch HW, van den Hove DLA, Kenis G, Lanfumey L. Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression. Psychopharmacology . 2018;235(8):2195.

5. How Untreated Depression Changes the Brain Over Time [Internet]. Psychology Today. [cited 2018 Oct 30]. Available from: https://www.psychologytoday.com/blog/neuronarrative/201804/how-untreated-depression-changes-the-brain-over-time

6. Mu Y E al. Signaling in adult neurogenesis. — PubMed — NCBI [Internet]. [cited 2018 Dec 8]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20471243/

7. Galea LA E al. Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications. — PubMed — NCBI [Internet]. [cited 2018 Dec 9]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23822747

8. Shohayeb B, Diab M, Ahmed M, Ng DCH. Factors that influence adult neurogenesis as potential therapy. Transl Neurodegener. 2018 Feb 21;7(1):4.

9. Mogi M E al. Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. — PubMed — NCBI [Internet]. [cited 2018 Dec 8]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10454142/

10. Molloy N, Read D, Gorman A. Nerve Growth Factor in Cancer Cell Death and Survival. Cancers . 2011 Feb 1;3(1):510–30.

11. Diniz BS E al. Reduced serum nerve growth factor in patients with late-life depression. — PubMed — NCBI [Internet]. [cited 2018 Dec 19]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23570892

12. View All Posts by. Nerve Growth Factor Stack — 3 Simple Ingredients to Boost Performance [Internet]. Nootropedia. 2017 [cited 2019 Jan 23]. Available from: https://www.nootropedia.com/nerve-growth-factor-stack/

13. Molendijk ML E al. Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=94… — PubMed — NCBI [Internet]. [cited 2018 Dec 15]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23958957/

14. Pandey GN E al. Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims. — PubMed — NCBI [Internet]. [cited 2018 Dec 15]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18611289

15. Björkholm C, Monteggia LM. BDNF — a key transducer of antidepressant effects. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26519901

16. Zhang JC E al. Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26786147

17. Erickson KI E al. The aging hippocampus: interactions between exercise, depression, and BDNF. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21531985

18. Diniz BS E al. Circulating Glial-derived neurotrophic factor is reduced in late-life depression. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21963280

19. Zhang X E al. Effect of treatment on serum glial cell line-derived neurotrophic factor in depressed patients. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18262703

20. Carvalho AF E al. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26210676/

21. Nowacka MM, Obuchowicz E. Vascular endothelial growth factor (VEGF) and its role in the central nervous system: a new element in the neurotrophic hypothesis of antidepressan… — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21719103

22. Sharma AN, da Costa e Silva BFB, Soares JC, Carvalho AF, Quevedo J. Role of trophic factors GDNF, IGF-1 and VEGF in major depressive disorder: A comprehensive review of human studies. J Affect Disord. 2016 Jun;197:9.

23. Szczęsny E E al. Possible contribution of IGF-1 to depressive disorder. — PubMed — NCBI [Internet]. [cited 2018 Dec 15]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24553010

24. Chigogora S E al. Insulin-like growth factor 1 and risk of depression in older people: the English Longitudinal Study of Ageing. — PubMed — NCBI [Internet]. [cited 2018 Dec 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27648920

25. Lir-Wan Fan YP. Dysregulation of neurogenesis by neuroinflammation: key differences in neurodevelopmental and neurological disorders. Neural Regeneration Res. 2017 Mar;12(3):366.

26. ScienceDirect [Internet]. [cited 2018 Dec 19]. Available from: https://www.sciencedirect.com/topics/medicine-and-dentistry/neuroinflammation

27. Tang MM E al. Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression. — PubMed — NCBI [Internet]. [cited 2018 Dec 19]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27106565

28. Lu M E al. Iptakalim confers an antidepressant effect in a chronic mild stress model of depression through regulating neuro-inflammation and neurogenesis. — PubMed — NCBI [Internet]. [cited 2018 Dec 21]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24621884

29. Genestine M, Lin L, Durens M, Yan Y, Jiang Y, Prem S, et al. Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in monoamine systems, forebrain structures and neurogenesis and behavior. Hum Mol Genet. 2015 Oct 15;24(20):5805.

30. Neurosci. Serotonin, depression, neurogenesis, and the beauty of science [Internet]. Neuroscientifically Challenged. [cited 2018 Dec 24]. Available from: https://www.neuroscientificallychallenged.com/blog/serotonin-depression-neurogenesis-beauty-of-science

31. Petroff OA. GABA and glutamate in the human brain. — PubMed — NCBI [Internet]. [cited 2018 Dec 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/12467378

32. Vicini S. The role of GABA and glutamate on adult neurogenesis [Internet]. https://physoc.onlinelibrary.wiley.com. 2008 [cited 2018 Dec 24]. Available from: https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2008.159046#references-section

33. Luscher B, Shen Q, Sahir N. The GABAergic Deficit Hypothesis of Major Depressive Disorder. Mol Psychiatry. 2011 Apr;16(4):383.

34. Rubio-Casillas A, Fernández-Guasti A. The dose makes the poison: from glutamate-mediated neurogenesis to neuronal atrophy and depression. — PubMed — NCBI [Internet]. [cited 2018 Dec 28]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27096778

35. Banaudha K, Marini AM. AMPA prevents glutamate-induced neurotoxicity and apoptosis in cultured cerebellar granule cell neurons. Neurotox Res. 2000 Mar 1;2(1):51–61.

36. SAGE Journals: Your gateway to world-class journal research [Internet]. SAGE Journals. [cited 2019 Jan 2]. Available from: https://journals.sagepub.com/doi/full/10.1177/1179069518779829

37. Kippin TE, Kapur S, van der Kooy D. Dopamine Specifically Inhibits Forebrain Neural Stem Cell Proliferation, Suggesting a Novel Effect of Antipsychotic Drugs. J Neurosci. 2005 Jun 15;25(24):5815–23.

38. Höglinger GU, Rizk P, Muriel MP, Duyckaerts C, Oertel WH, Caille I, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci. 2004 Jun 13;7(7):726.

39. Duman RS E al. Regulation of adult neurogenesis by antidepressant treatment. — PubMed — NCBI [Internet]. [cited 2018 Dec 24]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/11750177/

40. Wang JW E al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. — PubMed — NCBI [Internet]. [cited 2019 Jun 8]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18256257

41. 5-Bromo-2′-deoxyuridine B5002 [Internet]. Sigma-Aldrich. [cited 2019 Jan 9]. Available from: https://www.sigmaaldrich.com/catalog/product/sigma/b5002

42. Coradazzi M, Gulino R, Fieramosca F, Falzacappa LV, Riggi M, Leanza G. Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis. Neurobiology of Aging. 2016 Dec;48:93–102.

43. Bruel-Jungerman E E al. Cholinergic influences on cortical development and adult neurogenesis. — PubMed — NCBI [Internet]. [cited 2019 Jan 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/21272598

44. Mohapel P E al. Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning. — PubMed — NCBI [Internet]. [cited 2019 Jan 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15718053/

45. He X E al. Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion’s Mane) mushroom: A review. — PubMed — NCBI [Internet]. [cited 2019 Jan 23]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28087447

46. Friedman M. Chemistry, Nutrition, and Health-Promoting Properties of Hericium erinaceus (Lion’s Mane) Mushroom Fruiting Bodies and Mycelia and Their Bioactive … — PubMed — NCBI [Internet]. [cited 2019 Jan 23]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26244378

47. Tsai-Teng T E al. Erinacine A-enriched Hericium erinaceus mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1dE9 transgenic mice. — PubMed — NCBI [Internet]. [cited 2019 Jan 23]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27350344

48. Bishop A E al. Pyrroloquinoline quinone: a novel vitamin? — PubMed — NCBI [Internet]. [cited 2019 Jan 23]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/9810806

49. Liu S E al. Enhanced rat sciatic nerve regeneration through silicon tubes filled with pyrroloquinoline quinone. — PubMed — NCBI [Internet]. [cited 2019 Jan 23]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/15915445

50. Ostrovskaya RU E al. Noopept stimulates the expression of NGF and BDNF in rat hippocampus. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19240853

51. Antipova TA E al. Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27265136

52. Vakhitova YV, Sadovnikov SV, Borisevich SS, Ostrovskaya RU, Gudasheva TA, Seredenin SB. Molecular Mechanism Underlying the Action of Substituted Pro-Gly Dipeptide Noopept. Acta Naturae. 2016;8(1):82.

53. Dinoff A E al. The effect of acute exercise on blood concentrations of brain-derived neurotrophic factor in healthy adults: a meta-analysis. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28493624

54. Venezia AC E al. A single bout of exercise increases hippocampal Bdnf: influence of chronic exercise and noradrenaline. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28556463

55. De-Paula VJ E al. Long-term lithium treatment increases intracellular and extracellular brain-derived neurotrophic factor (BDNF) in cortical and hippocampal neurons … — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/27882645

56. Ricken R E al. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24018547

57. Leyhe T E al. Increase of BDNF serum concentration in lithium treated patients with early Alzheimer’s disease. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19276559

58. Fanaei H E al. Effect of curcumin on serum brain-derived neurotrophic factor levels in women with premenstrual syndrome: A randomized, double-blind, placebo-contr… — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26608718

59. Hurley LL E al. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF. — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23142609

60. Yu JJ E al. Chronic Supplementation of Curcumin Enhances the Efficacy of Antidepressants in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Cont… — PubMed — NCBI [Internet]. [cited 2019 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26066335

61. Dolotov OV E al. Semax, an analogue of adrenocorticotropin (4–10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal… — PubMed — NCBI [Internet]. [cited 2019 Feb 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16635254

62. Tsai SJ. Semax, an analogue of adrenocorticotropin (4–10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndr… — PubMed — NCBI [Internet]. [cited 2019 Feb 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16996699

63. Tajiri N E al. NSI-189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28181668

64. Mizuta, I., Ohta, M., Ohta, K., Nishimura, M., Mizuta, E., Hayashi, K. and Kuno, S. (2000). Selegiline and Desmethylselegiline Stimulate NGF, BDNF, and GDNF Synthesis in Cultured Mouse Astrocytes. Biochemical and Biophysical Research Communications, [online] 279(3), pp.751–755. Available at: https://www.sciencedirect.com/science/article/pii/S0006291X00940373 [Accessed 8 Mar. 2019].

65. Naoi M E al. Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms. — PubMed — NCBI [Internet]. [cited 2019 Feb 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23739004

66. de Tassigny XD, Pascual A, López-Barneo J. GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease. Front Neuroanat [Internet]. 2015 [cited 2019 Feb 10];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327623/

67. Jennifer S. Buell BD-H. Vitamin D and Neurocognitive Dysfunction: Preventing “D”ecline? Mol Aspects Med. 2008 Dec;29(6):415.

68. Sanchez B E al. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially rest… — PubMed — NCBI [Internet]. [cited 2019 Feb 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18816795

69. Xu SL E al. Flavonoids induce the synthesis and secretion of neurotrophic factors in cultured rat astrocytes: a signaling response mediated by estrogen receptor. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23878590

70. Caltagirone C, Cisari C, Schievano C, Di Paola R, Cordaro M, Bruschetta G, et al. Co-ultramicronized Palmitoylethanolamide/Luteolin in the Treatment of Cerebral Ischemia: from Rodent to Man. Transl Stroke Res. 2016 Feb 1;7(1):54–69.

71. Chen WJ E al. Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28964807

72. Moore A E al. Resveratrol and Depression in Animal Models: A Systematic Review of the Biological Mechanisms. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30200269

73. Ge L E al. Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26485503

74. Skaper SD E al. N-Palmitoylethanolamine and Neuroinflammation: a Novel Therapeutic Strategy of Resolution. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26055231

75. Skaper SD E al. Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23813098

76. Scuderi C E al. Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-ac… — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22405189

77. Mandolini GM E al. Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29789034

78. Marchalant Y E al. Cannabinoids attenuate the effects of aging upon neuroinflammation and neurogenesis. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19385063

79. Campos AC, Ortega Z, Palazuelos J, Fogaça MV, Aguiar DC, Díaz-Alonso J, et al. The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system. Int J Neuropsychopharmacol. 2013 Jul 1;16(6):1407–19.

80. Huang L E al. Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29243061

81. Cai J E al. Curcumin mitigates cerebral vasospasm and early brain injury following subarachnoid hemorrhage via inhibiting cerebral inflammation. — PubMed — NCBI [Internet]. [cited 2019 Mar 17]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/28948084

82. Candelario M E al. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26068424

83. Singh N E al. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/22754076

84. Savage K E al. GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence. — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29168225

85. Rosalie Awad Asim Muhammad Tony Durst Vance L. Trudeau John T. Arnason. Bioassay‐guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity [Internet]. Wiley Online Library. 2009 [cited 2019 Mar 20]. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.2712

86. Schmaal L, Veltman DJ, Nederveen A, van den Brink W, Goudriaan AE. N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study. Neuropsychopharmacology. 2012 Aug;37(9):2143.

87. Das P E al. Metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking N-acetyl-cysteine versus placebo. — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23341476

88. Chaki S, Fukumoto K. Potential of Glutamate-Based Drug Discovery for Next Generation Antidepressants. — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26393618

89. Strzelecki D E al. Supplementation of antipsychotic treatment with sarcosine — GlyT1 inhibitor — causes changes of glutamatergic (1)NMR spectroscopy parameters in the… — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26306650

90. Xue X-C, Wu Y-J, Gao M-T, Li W-G, Zhao N, Wang Z-L, et al. Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats. World J Gastroenterol. 2004 Apr 1;10(7):1032.

91. Sikiric P E al. Gastric mucosal lesions induced by complete dopamine system failure in rats. The effects of dopamine agents, ranitidine, atropine, omeprazole and p… — PubMed — NCBI [Internet]. [cited 2019 Mar 20]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/10791690/

92. Sharma A, Gerbarg P, Bottiglieri T, Massoumi L, Carpenter LL, Lavretsky H, et al. S-Adenosylmethionine (SAMe) for Neuropsychiatric Disorders: A Clinician-Oriented Review of Research. J Clin Psychiatry. 2017 Jun;78(6):e656.

93. Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. — PubMed — NCBI [Internet]. [cited 2019 Mar 21]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/18950248/

94. The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons at cerebral hippocampus of depressive rats. Phytomedicine. 2009 Sep 1;16(9):830–8.

95. Rajan KE E al. Molecular and Functional Characterization of Bacopa monniera: A Retrospective Review. — PubMed — NCBI [Internet]. [cited 2019 Jun 7]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26413131

96. Chatterjee M E al. Antipsychotic activity of standardized Bacopa extract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopa… — PubMed — NCBI [Internet]. [cited 2019 Jun 7]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25856700

97. van Diermen D, Marston A, Bravo J, Reist M, Carrupt P-A, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. Journal of Ethnopharmacology [Internet]. 2009 Mar [cited 2019 Jul 13];122(2):397–401. Available from: https://www.sciencedirect.com/science/article/pii/S037887410900021X

98. Effect of choline-containing phospholipids on brain cholinergic transporters in the rat. J Neurol Sci. 2011 Mar 15;302(1–2):49–57.

99. Traini E E al. Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline- containing phospholipid with a still interesting profile as cognition enha… — PubMed — NCBI [Internet]. [cited 2019 Jun 7]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24156263

100. Taglialatela G E al. Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. — PubMed — NCBI [Internet]. [cited 2019 Jun 7]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/8187841

101. Carta A E al. Acetyl-L-carnitine and Alzheimer’s disease: pharmacological considerations beyond the cholinergic sphere. — PubMed — NCBI [Internet]. [cited 2019 Jun 7]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/8239306

2 thoughts on “Link to depression and brain changes — Part 2

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s