Microglia, Astrocytes, Behavior

Unit 2 Reading Guide 1

Glial cells

Non-neuronal cells of the CNS that support, regulate, and actively shape neural function and behavior. Major types include astrocytes, microglia, and oligodendrocytes. Once considered passive, ___ are now recognized as essential for synaptic development, metabolic homeostasis, immune signaling, and behavior

Astrocytes

Star-shaped glial cells that contact hundreds of thousands of synapses and blood vessels. They regulate neurotransmission, metabolism, ion balance, synapse formation, plasticity, and blood–brain barrier function. ___ are active participants in cognition and behavior, not just structural support cells

Microglia

The brain’s resident innate immune cells. They originate early in development and sculpt neural circuits by phagocytosing synapses, regulating neurogenesis, releasing cytokines and trophic factors, and monitoring brain homeostasis. Dysfunctional ___ can directly cause behavioral pathology

Oligodendrocytes

Glial cells that form myelin sheaths around axons, enabling fast and efficient electrical conduction. They also influence axonal integrity and neural circuit function, and their development is supported by microglia and astrocytes during development

Glial scar

A reactive structure formed primarily by astrocytes after CNS injury. It isolates damaged tissue but can also inhibit axon regeneration. It reflects a shift in astrocytes toward a reactive (gliotic) state

Gliosis

A reactive response of glial cells (astrocytes and microglia) characterized by hypertrophy, proliferation, and altered gene expression following injury, inflammation, or disease. ___ can be protective or pathological depending on context

Vasoconstriction

Narrowing of blood vessels, reducing blood flow. Astrocytes influence ___ through signaling at the neurovascular unit, coupling neural activity to blood supply

Vasodilation

Widening of blood vessels to increase blood flow. Astrocytes detect neuronal activity and signal capillaries to deliver glucose and oxygen to active neurons

Alexander’s disease

A rare genetic neurodevelopmental disorder caused by mutations in GFAP, leading to astrocyte dysfunction. Results in macrocephaly: abnormally large head size due to abnormal astrocyte accumulation and white-matter pathology

Alzheimer’s disease

A neurodegenerative disorder characterized by cognitive decline and neuronal loss. Characterized by amyloid beta: toxic peptide that accumulates in plaques; astrocytes normally clear amyloid beta but become overwhelmed, contributing to neuronal death

Parkinson’s disease

A neurodegenerative disorder involving loss of dopaminergic neurons and substantia nigra. Glial dysfunction (astrocytic metabolic failure and microglial inflammation) contributes to neuronal vulnerability and disease progression

Free radicals

Reactive oxygen and nitrogen species (ROS/RNS) that damage proteins, lipids, and DNA. Astrocytes normally protect neurons by scavenging ___; loss of this function leads to neuronal death

Glutamate

The primary excitatory neurotransmitter in the CNS. Astrocytes regulate ___ levels by uptake and recycling; failure leads to excitotoxicity and neuronal damage

Trophic factors

Molecules that support neuron survival, growth, and plasticity (e.g., BDNF, IGF-1). Both astrocytes and microglia release trophic factors during development and learning

Erythropoietin

A cytokine with neuroprotective and anti-inflammatory properties; glial cells can produce ___-like factors that promote neuronal survival under stress

Main functions of microglia

Synaptic pruning (elimination of weak or excess synapses), phagocytosis of cells, debris, and synaptic elements, regulation of neurogenesis and cell survival, release of cytokines and growth factors, and shaping neural circuits underlying behavior

When microglia populate the brain + when their populations stabilize

Colonization begins around embryonic day (E) 8–9. Proliferate locally after birth, peak density occurs around postnatal day (P) 14, adult-like stable numbers by P28

When microglial recolonization occurs in mature brain

occurs after irradiation, chronic stress, or blood–brain barrier disruption. These invading cells are peripheral immune-derived macrophages, which differ molecularly and functionally from embryonically derived ___

Selective roles of astrocytes

Calcium signaling networks (astrocyte-astrocyte communication), modulation of synaptic transmission (tripartite synapse), and metabolic support of neurons, including glucose delivery and waste removal

Physiological processes that astrocytes regulate

Synapse formation and plasticity, neuronal migration during development, neurogenesis (developmental and adult), blood–brain barrier integrity, ion homeostasis, and redox balance and antioxidant defense

Behaviors astrocytes support

Learning and memory (LTP), sleep and circadian rhythms, sexual behavior, motor function, cognitive flexibility

Neurological disorders involving astrocyte dysfunction

Alexander disease, Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), Rett syndrome, Fragile X syndrome, Cerebellar ataxias

Protective astrocyte secretions

Antioxidants (ROS/RNS scavenging), trophic factors (BDNF, IGF-1), glutamate uptake, metabolic support

Deleterious (when dysregulated) astrocyte secretions

Excess glutamate, pro-inflammatory cytokines, failure of redox control leading to oxidative stress. Loss of astrocytic redox regulation alone causes neuronal death and motor deficits