Document text
Principal Investigator: Junsung Woo
Organization: BAYLOR COLLEGE OF MEDICINE
Fiscal Year: 2024
Award: $608,297
Funding agency: National Institute of Mental Health
Summary
Astrocytes are the most abundant type of glial cell in the brain, playing vital roles in all facets of brain physiology.
Given their central role in brain function, astrocytes have been implicated in a variety of psychiatric disorders
including autism, anxiety, schizophrenia, depression, and suicide. Despite the progress in understanding the
abnormalities in brain circuits and related molecular pathways, how astrocytes contribute to circuit dysfunction
associated with psychiatric disorders remains nascent. Recent studies have shown that astrocytes play an
essential role in amygdala function and associated behavioral outputs, which led us to further examine how
amygdala astrocytes contribute to human depression and associated suicide. Towards this, we performed
immunostaining from suicide decedents (N=20) and age-matched control, finding that the canonical astrocyte
marker GFAP and a key astrocyte transcription factor NFIA are both drastically increased in the amygdala of
suicide decedents. Recently, we reported that NFIA plays an essential role in the physiological activities of
astrocytes, neuronal circuit activity, and brain function in the adult hippocampus. This evidence led us to
hypothesize that astrocytic NFIA contributes to depression and associated suicide by regulating amygdala circuit
function. To determine whether astrocytic NFIA affects amygdala circuit function and associated depressive
behaviors, we utilized NFIA gain-of-function (GOF) and loss-of-function (LOF) mouse models. Preliminary
studies revealed that NFIA GOF induced depressive/anxiety behaviors, while NFIA LOF suppressed these
behaviors. In both cases, direct physiological analysis of amygdala circuit activity revealed significant and
complementary alterations.
Therefore, based on the strength of these preliminary data, we propose the following specific aims. In
specific aim 1, we will determine the role of astrocytic NFIA in amygdala circuit activity and function using NFIA
GOF and LOF mice models. In specific aim 2, we will decipher how astrocytic NFIA regulates amygdala circuits
through GABA/MAOB. In this study, we will identify the target gene of NFIA using RNA-sequencing and
manipulate the target gene with pharmacological/genetic tools. In specific aim 3, we will delineate astrocytic
NFIA transcriptional networks in the amygdala. In this study, we will dissect the amygdala-specific NFIA
transcriptional networks and confirm this in human samples.
Terms: <21+ years old><4-Aminobutanoic Acid><4-Aminobutyric Acid><4-amino-butanoic acid><ASD><Adult><Adult Human><Affect><Age><Aminalon><Aminalone><Ammon Horn><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anxiety><Astrocytes><Astrocytus><Astroglia><Astroprotein><Autism><Autistic Disorder><Automobile Driving><Autoregulation><Basal Transcription Factor><Basal transcription factor genes><Behavior><Behavioral><Blood flow><Brain><Brain Nervous System><Brain region><Cell Nucleus><ChIP Sequencing><ChIP-seq><ChIPseq><Cornu Ammonis><Data><Depressed mood><Depressive Syndromes><Depressive disorder><Dysfunction><Early Infantile Autism><Emotional Depression><Emotions><Encephalon><Enzyme Gene><Enzymes><Functional disorder><GABA><GFA-Protein><GFAP><Gene Expression><Gene Transcription><General Transcription Factor Gene><General Transcription Factors><Genes><Genetic><Genetic Transcription><Glia><Glial Cells><Glial Fibrillary Acid Protein><Glial Fibrillary Acidic Protein><Glial Intermediate Filament Protein><Goals><Hippocampus><Homeostasis><Human><Infantile Autism><KIAA1439><Kanner's Syndrome><Knock-out><Knockout><Kolliker's reticulum><Link><MAO-B><Measures><Mental Depression><Mental disorders><Mental health disorders><Metabolic><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Monoamine Oxidase B><Morphology><Murine><Mus><NFIA><NFIA gene><Nerve Cells><Nerve Unit><Neural Cell><Neural Transmission><Neurocyte><Neuroglia><Neuroglial Cells><Neurons><Non-neuronal cell><Nonneuronal cell><Nuclear Factor I/A><Nucleus><Output><Pathway interactions><Physiologic><Physiological><Physiological Homeostasis><Physiology><Physiopathology><Play><Psychiatric Disease><Psychiatric Disorder><Psychiatric therapeutic procedure><RNA Expression><RNA Seq><RNA sequencing><RNAseq><Regulation><Reporting><Role><Sampling><Schizophrenia><Schizophrenic Disorders><Suicide><Synaptic Transmission><Transcription><Transcription Factor NFIA><Transcription Factor Proto-Oncogene><Transcription factor genes><Type B Monoamine Oxidase><adulthood><ages><amygdaloid nuclear complex><anxious behavior><astrocytic glia><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><chromatin immunoprecipitation-sequencing><dementia praecox><depressed><depression><depression symptom><depressive><depressive behavior><depressive symptoms><driving><excitatory neuron><fatal attempt><fatal suicide><gain of function><gamma-Aminobutyric Acid><gene network><genetic approach><genetic strategy><hippocampal><inhibitory neuron><intent to die><loss of function><mental illness><mouse model><murine model><nerve cement><neuronal><neuronal circuit><neuronal circuitry><neuronal excitability><pathophysiology><pathway><pharmacologic><promoter><promotor><prospective><psychiatric care><psychiatric illness><psychiatric therapy><psychiatric treatment><psychological disorder><sadness><schizophrenic><social role><suicides><tool><transcription factor><transcriptome sequencing><transcriptomic sequencing><γ-Aminobutyric Acid>