# Astrocyte bioenergetics in brain development network activity and cognition

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $468,238

## Abstract

Project Summary
 Deficits in astrocyte energy supply could lead to abnormal neuronal function and cognitive
 impairment consistent with aspects of major psychiatric disorders. Patients with schizophrenia and bipolar
 disorder demonstrate signs of mitochondria dysfunction and metabolic alterations. The mechanisms of these
 metabolic changes remain obscure. Recent GWA studies have implicated several genetic risk factors in
 mitochondria bioenergetics in astrocytes.
 We will study how abnormal mitochondria respiration and glutamate metabolism in astrocytes
 produced by the highly penetrant astrocyte genetic risk factors, Neuronal PAS domain protein 3 (NPAS3)
 and its transcriptional target, a 22q.11 CNV gene, SLC2518A, will affect the morphology and physiology of
 vulnerable parvalbumin-positive (PV+) neurons of prefrontal cortex to impair cognitive function in a time and
 brain region-dependent manner.
 We hypothesize that abnormalities in this metabolic pathway in astrocytes will lead to a chronic
increase in glutamate secretion that, in turn, will affect neuronal and cognitive functions in a time-dependent
and brain circuit-related manner.
 Specific Aim 1 will determine the molecular mechanisms of NPAS3 transcriptional regulation of
SLC25A18 in astrocytes.
 Specific Aim 2 will determine the role of NPAS3-SLC25A18 interplay in mitochondria respiration and
glutamate metabolism in astrocytes.
 Specific Aim 3 will determine the contributions of metabolic alterations in astrocytes to time- and brain
circuit-dependent neuronal and cognitive dysfunction.
 Our studies will advance our understanding of how genetic risks factors influence the key metabolic
pathways in astrocytes, leading to abnormal energy and glutamate homeostasis, deficient inhibitory activity of
cortical PV+ neurons and cognitive impairment.

## Key facts

- **NIH application ID:** 10182414
- **Project number:** 7R01MH083728-10
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Mikhail V Pletnikov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $468,238
- **Award type:** 7
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10182414

## Citation

> US National Institutes of Health, RePORTER application 10182414, Astrocyte bioenergetics in brain development network activity and cognition (7R01MH083728-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10182414. Licensed CC0.

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