bims-adhine 2026-08-23 papers

Issue of 2026–08–23
three papers selected by
Tamara J. Buijs, Universiteit van Amsterdam

Neuroscience. 2026 Aug 21. pii: S0306-4522(26)00574-9. [Epub ahead of print]

Effects of testosterone upon the survival of new neurons in the dentate gyrus of adult male rats.

Tatum W Hamilton, Ezra J LeMole, Grace K Nadecki, Jordan M Gardner, Quinn P Kennedy, Kathryn A Blek, Mark D Spritzer.

Prolonged testosterone exposure promotes adult hippocampal neurogenesis, but it remains unclear whether exposure during specific time periods of neural development is necessary for testosterone to enhance neuron survival. Our experiment tested the effects of testosterone on the later stages of neural development, when functional synapses are forming. Adult male rats (n = 7-8/group) were bilaterally castrated and given a single injection of bromodeoxyuridine (BrdU; 200 mg/kg). Daily injections of testosterone (0.500 mg/rat) or sesame oil (0.1 ml/rat) were given 1-30, 1-15, or 16-30 days after BrdU injection. BrdU-labeled cells were quantified using immunohistochemistry and light microscopy. BrdU/NeuN fluorescent double-labeling followed by confocal microscopy was used to quantify the percentage of new cells that were neurons. For the entire dentate gyrus, testosterone injections during days 1-30 significantly increased the number of BrdU-labeled cells, whereas the other time periods did not. Within the dorsal dentate gyrus, injections during both 1-30 and 16-30 days after cell proliferation resulted in an increased number of BrdU-labeled cells. No effects of testosterone were observed in the ventral dentate gyrus. Confocal microscopy confirmed that a majority (about 80%) of BrdU-labeled cells differentiated into neurons regardless of treatment. Our results support previous findings that prolonged testosterone exposure is needed to increase hippocampal neurogenesis and suggest that the later stage of neuronal development (i.e., 16-30 days old) is more sensitive to testosterone than earlier stages. Given the potential benefits of adult neurogenesis for treating neurodegenerative conditions, our results suggest that androgens may have therapeutic value.

Keywords: Androgen; Dentate gyrus; Hippocampus; Neurogenesis; Rat; Testosterone

DOI: https://doi.org/10.1016/j.neuroscience.2026.08.031

Nat Med. 2026 Aug 21.

Dysregulated adult hippocampal neurogenesis in major depressive disorders.

Major depressive disorder (MDD) is associated with reduced hippocampal volume, altered connectivity and negative memory bias, suggesting disrupted hippocampal plasticity. Dysregulated adult hippocampal neurogenesis is a potential contributor, but its relevance in humans and role in MDD remain unclear. Here we investigated the molecular basis of hippocampal dysfunction in nonmedicated individuals with MDD by integrating analyses of neurogenic trajectories, cell-type- and subfield-specific gene expression, chromatin accessibility and protein expression. We identify a neurogenic lineage in the adult human hippocampal subgranular zone and provide evidence for a stalled neurogenic process in MDD, associated with transcriptional regulation, stress-related reprogramming and interferon signaling across developmental stages. Excitatory and inhibitory neurons show dysregulation of transcription factor networks affecting cell states. Cellular stress, excitatory-inhibitory imbalance, impaired synaptic plasticity, reduced metabolic capacity and immune activation, underlie impaired neurogenesis and reduced hippocampus circuit plasticity. Findings indicate genetic and epigenetic regulation of gene expression in MDD, and overlapping pathogenetic mechanisms with autoimmune, neurodevelopmental and neurodegenerative diseases. This work provides a new understanding of the pathogenesis of hippocampus-dependent cognitive symptoms in MDD and suggests potential therapeutic targets.

DOI: https://doi.org/10.1038/s41591-026-04571-8

Cell Rep. 2026 Aug 20. pii: S2211-1247(26)00958-7. [Epub ahead of print]45(9): 117880

Newborn neurons compete with neuronal ensembles to moderate behavioral responses to stress.

Can-Yuan Zhang, Su-Fen Wei, Ya-Ping Wang, Jia-Qi Nie, Qi Wang, Fu-Ling Wu, Ming-Feng Huang, Wei-Zhong Cai, Liang-Yu Chen, Jin-Ming Liu, Fang Guo, Xiao-Shan Lin, Shu-Ji Li, Xiang-Na Guo, Si-Qiang Ren, Xiong Cao.

Newborn neurons in the adult hippocampal dentate gyrus (DG) are hyperexcitable, competitive cells involved in behavioral responses to stress and antidepressants. The role and the mechanisms underlying the competitiveness of the newborn neurons in moderating behavioral responses to stress have not yet been comprehensively investigated. Using FosTRAP2 transgenic mice in the learned helplessness (LH) paradigm, we report that voluntary running, a guideline-supported intervention for depression, induces neurogenesis, and that the newly generated neurons compete with LH-TRAPed neurons, thereby reducing stress-induced helpless behavior. Mechanistically, we found that increasing neurogenesis is sufficient to reduce spine density in LH-TRAPed neurons via p21-activated kinase 4 (Pak4) and to attenuate Ca2+ activity in these neurons. Taken together, our findings suggest that highly excitable newborn neurons compete with LH-TRAPed neurons, attenuating helpless behaviors and providing therapeutic value for depressed individuals, who typically show enhanced memory for negative events.

Keywords: CP: neuroscience; adult hippocampal neurogenesis; depression; helpless behavior; neuronal ensembles; resilience; stress

DOI: https://doi.org/10.1016/j.celrep.2026.117880