bims-adhine 2026-07-26 papers

Issue of 2026–07–26
three papers selected by
Tamara J. Buijs, Universiteit van Amsterdam

Mol Psychiatry. 2026 Jul 21.

Role of hippocampal dentate granule cells in memory: neuronal birth timing matters.

The dentate gyrus is a critical hub for hippocampal-dependent memory and is distinguished by its capacity for lifelong neurogenesis, resulting in a heterogeneous population of granule cells generated across embryonic, postnatal, adolescent, and adult stages. Although extensive work has examined the functional contributions of immature adult-born granule cells, whether granule cells born at different life stages retain distinct functional roles once they reach maturity has remained largely unexplored. In this review, we synthesize findings from anatomical, physiological, and behavioral studies that, while not designed to address this question directly, collectively support the proposal that temporal origin constitutes a previously underappreciated organizing principle of dentate gyrus function. We argue that neurons born at different life stages differ not only in their morphological and electrophysiological properties but in the distinct aspects of memory functions they support. Understanding how neuronal birth timing shapes hippocampal computation across the lifespan may have broader implications for conditions in which memory is compromised, from cognitive aging to neuropsychiatric and neurodegenerative disorders, and we hope this framework encourages the more systematic, temporally precise investigations that will be needed to explore them.

DOI: https://doi.org/10.1038/s41380-026-03745-7

Semin Cell Dev Biol. 2026 Jul 20. pii: S1084-9521(26)00019-4. [Epub ahead of print]183 103685

Adult neural stem cell pools in homeostasis and pathogenesis.

Si Li, Xiang Shi, Xue-Lian Sun, Qing-Feng Wu.

Adult neural stem cells (NSCs) persist throughout life in discrete neurogenic niches of the mammalian brain, most prominently the subventricular zone (SVZ), the subgranular zone (SGZ) of the hippocampal dentate gyrus, and the hypothalamic ventricular zone (HVZ). These niches harbor regionally specialized NSC populations that support neural plasticity, cognitive and emotional regulation, and, in the hypothalamus, systemic metabolic and neuroendocrine homeostasis. While adult neurogenesis in the SGZ and SVZ has been extensively characterized, the HVZ has emerged as a functional adult NSC niche linking stem cell regulation to whole-body physiology. Here, we review recent advances across the SGZ, SVZ, and HVZ to define shared organizational principles and region-specific regulatory mechanisms governing adult NSC identity, homeostasis, and lineage output. We also highlight how intrinsic transcriptional programs, metabolic states, and niche-derived signals shape NSC behavior in each region, and how aging, inflammation, and metabolic stress differentially disrupt these processes. By integrating insights from both classical and hypothalamic neurogenic niches, this review provides a unified framework for understanding adult NSC diversity and disease susceptibility, and discusses strategies to modulate endogenous stem cell niches to preserve homeostasis and minimize disease risk.

Keywords: Homeostasis; Hypothalamus; Neural stem cells; Pathogenesis; Subgranular zone; Subventricular zone

DOI: https://doi.org/10.1016/j.semcdb.2026.103685

J Pharmacol Sci. 2026 Sep;pii: S1347-8613(26)00039-3. [Epub ahead of print]162(1): 80-88

Chronic glucocorticoid exposure disrupts lactate homeostasis and hippocampal neurogenesis by reducing cerebrovascular monocarboxylate transporter 1, leading to behavioral abnormalities in mice.

Ayami Kita-Shirakura, Kaede Ishihara, Nagisa Kimura, Momoka Tanida, Ryota Araki, Takeshi Yabe.

Prolonged glucocorticoid elevation is strongly associated with brain dysfunction and the pathogenesis of stress-related disorders, including several psychiatric disorders. Elevated lactate levels have been reported in the brains of patients with psychiatric disorders and animal models of chronic stress and psychiatric disorders. Prolonged glucocorticoid elevation may disrupt brain lactate homeostasis, but the mechanisms through which this occurs and the pathological significance of the disruption are incompletely understood. Here, we show that chronic corticosterone (CORT) treatment increases lactate in the hippocampus and reduces monocarboxylate transporter 1 (MCT1) expression in hippocampal cerebrovascular endothelial cells. Cerebrovascular-specific overexpression of MCT1 reduced hippocampal lactate accumulation and ameliorated impaired hippocampal neurogenesis, depression-like behavior, and cognitive impairment in chronically CORT-treated mice. Conversely, knockdown of cerebrovascular MCT1 expression increased lactate accumulation in the hippocampus and caused impaired hippocampal neurogenesis and cognitive impairment. These findings suggest that chronic glucocorticoid elevation induces lactate accumulation via dysregulation of cerebrovascular lactate transport, thereby impairing neurogenesis and inducing behavioral abnormalities. This mechanism may contribute to stress-related brain dysfunction and the pathogenesis of psychiatric disorders.

Keywords: Cognitive impairment; Depression; Lactate; Monocarboxylate transporter 1; Neurogenesis

DOI: https://doi.org/10.1016/j.jphs.2026.07.001