bims-adhine 2026-09-20 papers

Biology (Basel). 2026 Sep 04. pii: 1536. [Epub ahead of print]15(17):

BDNF Haploinsufficiency Limits Voluntary Exercise-Induced Adult Hippocampal Neurogenesis.

Monique Klausch, Jens Schepers, Viola von Bohlen Und Halbach, Oliver von Bohlen Und Halbach.

Adult hippocampal neurogenesis is involved in hippocampal plasticity and can be enhanced by voluntary physical activity, which also elevates "brain-derived neurotrophic factor" (BDNF) levels and improves memory performance. BDNF might either be essential for the maintenance of neurogenesis, or be necessary for mediating activity-dependent increases in neurogenesis. In order to get more insight on this, we examined male heterozygous BDNF-deficient (BDNF +/-) mice with or without access to a running wheel. Only males were analyzed, since sex steroids can interact with BDNF signaling pathways. Although male BDNF +/- mice exhibited a higher body weight as compared to age-matched controls (BDNF +/+), they did not differ in distance traveled, running time or running speed. We then analyzed whether changes in adult hippocampal neurogenesis can be observed. Under housing conditions without running wheels, the rates of basal adult hippocampal neurogenesis were not altered between genotypes. Interestingly, voluntary wheel running significantly increased neurogenesis in both groups; however, the magnitude was attenuated in BDNF +/- mice. These results indicate that, in adult male mice, reduced BDNF availability does not impair basal adult hippocampal neurogenesis, but limits the plasticity-related enhancement of neurogenesis induced by physical activity.

Keywords: BDNF; doublecortin; neurogenesis; neuronal plasticity; running wheel; voluntary exercise

DOI: https://doi.org/10.3390/biology15171536

J Alzheimers Dis. 2026 Sep 16. 13872877261487394

L-serine-enriched diet restores impaired adult neurogenesis in the hippocampus of 3xTg-AD mice.

Brainbank Neuro-CEB Neuropathology Network 5

BackgroundAltered adult neurogenesis occurs in Alzheimer's disease (AD) in humans and rodent models, though the mechanisms remain unclear. L-serine, a non-essential amino acid critical for cell proliferation and survival, is produced by neuroepithelial cells and radial glia in the developing brain, and by astrocytes and neural precursors in the adult brain. Its production is altered in AD, particularly in the hippocampus.ObjectiveTo determine whether reduced L-serine availability contributes to impaired adult neurogenesis in AD.MethodsWe examined the expression of phosphoglycerate dehydrogenase (PHGDH), an enzyme in L-serine biosynthesis, in neural stem cells (NSCs) of mouse and human dentate gyrus (DG). Adult neurogenesis was assessed by quantifying proliferating neural precursors and immature neurons in 7- and 12-month-old 3xTg-AD mice and age-matched controls. Mice received an L-serine-enriched diet for 4 or 8 months, after which plasma serine levels, neurogenesis markers, and amyloid pathology were evaluated.ResultsPHGDH was expressed by NSCs in the mouse DG and by cells in the subgranular zone (SGZ) of the human DG showing radial morphology typical of rodent NSCs. Twelve-month-old 3xTg-AD mice showed a significant reduction in proliferating (PCNA-positive) precursors and immature (DCX-positive) neurons in the DG relative to controls. L-serine supplementation significantly raised plasma L- and D-serine levels and partially rescued neurogenesis deficits in 3xTg-AD mice, without affecting amyloid pathology.ConclusionsWe suggest that impairment of L-serine metabolism and the resulting reduction in D-serine availability contributes to impaired adult neurogenesis, potentially via reduced survival of newborn neurons in the DG of 3xTg-AD mice.

Keywords: Alzheimer's disease; L-serine; adult neurogenesis; energy metabolism; glia; hippocampus; neural precursors

DOI: https://doi.org/10.1177/13872877261487394

Mol Psychiatry. 2026 Sep 17.

Reconciling the neurogenic hypothesis of depression with recent advances in adult hippocampal neurogenesis research in humans.

Sophie Simard, Naguib Mechawar.

Depression is a highly prevalent mood disorder with a complex etiology that has yet to be fully characterized. Alterations in the generation of new granule neurons in the hippocampal dentate gyrus have been hypothesized to contribute to the pathophysiology of depression and recovery from this mood disorder, a theory coined the "neurogenic hypothesis of depression". This article revisits current evidence of this hypothesis in humans, which reveals varying perspectives from post-mortem studies. Drawing on recent findings in the field of human adult hippocampal neurogenesis, we also offer here potential research directions regarding how immature granule neurons, which have been so far understudied in this context, may be affected in the pathogenesis of depression. Finally, this review explores to what extent immature granule neurons are involved in the neurobiological basis of this mood disorder and how their properties may increase their vulnerability to stress-mediated changes in the hippocampus. Together, this review provides crucial insight into immature granule neurons as a particularly interesting therapeutic target to mitigate stress-related behavioural impairments.

DOI: https://doi.org/10.1038/s41380-026-03896-7

Int J Mol Sci. 2026 Aug 25. pii: 7607. [Epub ahead of print]27(17):

Deiodinase 3 Deficiency Impairs Hippocampal and Lateral Ventricle Neurogenesis in Middle-Aged Female Mice.

Zhaofei Wu, M Elena Martinez, Arturo Hernandez.

Thyroid hormone (TH, the active metabolite T3)) plays a critical role in neuronal proliferation and differentiation during development. However, its role in adult neurogenesis (ANG) remains incompletely understood. To gain insight into the role of T3 in ANG, we used a mouse model (Dio3KO mouse) with a deficiency in type 3 deiodinase, which clears T3 in the brain. We observed that the number of DCX/RBFOX3 double-positive cells is significantly reduced in the subgranular zone (SGZ) and the subventricular zone (SVZ) of 10-month-old female Dio3KO mice, suggesting impaired ANG in these neurogenic niches. However, no significant changes were observed in IBA1/GFAP or OLIG2/GFAP double-positive cells, suggesting that the neurogenic deficits are not associated with neuroinflammation, gliosis, or altered oligodendrogenesis. Cortical RNA-seq analysis further identified dysregulated T3-responsive genes implicated in ANG, revealing marked sex-dependent differences in gene expression. Proof-of-concept experiments in type 2 deiodinase 2 (Dio2) and Dio3 double knockout mice revealed a rescue of the neurogenic phenotype, supporting the hypothesis that loss of DIO2-mediated T3 generation counteracts the detrimental effects of DIO3 deficiency on ANG. Collectively, these findings identify DIO3- and DIO2-me fotmdiated T3 homeostasis in neural cells as critical contributors to T3-dependent ANG in females, with implications for neurodegenerative diseases and their sexually dimorphic prevalence.

Keywords: adult neurogenesis; deiodinase 3 (DIO3); sexual dimorphism; subgranular zone (SGZ); subventricular zone (SVZ); thyroid hormone

DOI: https://doi.org/10.3390/ijms27177607

NPJ Aging. 2026 Sep 17. pii: 124. [Epub ahead of print]12(1):

Effects of a three-month exercise programme on cognition, mood and neurogenesis: the NeuroFit randomised controlled trial.

Sahand Farmand, Curie Kim, Andrea Du Preez, André O Werneck, Lucia Batzu, Dominic Pearce, Kirsten Brady, Markos Khir, Sarah Nicolas, John F Cryan, Yvonne M Nolan, Brendon Stubbs, Sandrine Thuret.

Middle age represents a critical window for mental and cognitive change, yet it remains relatively understudied as a target period for preventative lifestyle interventions. We conducted a three-month randomised controlled trial in healthy middle-aged adults in the UK (n = 52) to examine the effects of exercise on pattern separation, cognition and well-being, blood-based biomarkers, and hippocampal neurogenesis, using an in vitro parabiosis assay. No significant intervention-by-time effect was observed for the primary outcome, pattern separation (β = 0.33, p = 0.26). However, significant intervention-by-time effects were detected for depressive symptoms, as measured by the PHQ-9 (β = -1.18, adjusted p = 0.011), and for the percentage of proliferative cells in vitro (β = -0.23, adjusted p = 0.02), suggesting that exercise remodels the circulating milieu in ways that directly influence hippocampal progenitor biology. Overall, our findings suggest that a structured, instructor-led, live online exercise programme in midlife is feasible and may produce temporally staged adaptations, with early effects on mood, intermediate systemic biological changes influencing hippocampal progenitor dynamics, and cognitive benefits that may require longer exposure to emerge. The trial was prospectively registered at Clinicaltrials.gov ( NCT05397990 ).

DOI: https://doi.org/10.1038/s41514-026-00439-w