Microglia of Prefrontal White Matter in Suicide

Abstract

Immune functions in the brain are associated with psychiatric illness and with temporary alteration of mental state. Microglia, the principal brain immunological cells, respond to changes in the internal brain milieu through a sequence of activated states, each with characteristic function and morphology. To assess a possible association of frontal white matter pathology with suicide, autopsy brain tissue samples from 11 suicide and 25 non-suicide subjects were stained for ionized calcium-binding adapter molecule 1 (Iba-1), CD68, and myelin. Groups were matched by age, sex, and psychiatric diagnosis. We classified Iba-1-immunoreactive cells on the basis of shape, immunoreactivity for CD68, and association with blood vessels to obtain stereologic estimates of densities of resting microglia, activated phagocytes, and perivascular cells. We found no effect of psychiatric diagnosis but 2 statistically significant effects of suicide: 1) the dorsal-ventral difference in activated microglial density was reversed such that with suicide, the density was greater in ventral than in dorsal prefrontal white matter, whereas in the absence of suicide, the opposite was true; and 2) with suicide there was a greater density of Iba-1-immunoreactive cells within or in contact with blood vessel walls in dorsal prefrontal white matter. These observations could reflect a mechanism for the stress/diathesis (state/trait) model of suicide whereby an acute stress activates a reactive process in the brain, either directly or by compromising the blood-brain barrier, and creates a suicidal state in an individual at risk. They also indicate the theoretical potential of imaging studies in live, vulnerable individuals for the assessment of suicide risk. Further studies are needed to investigate specific phenotypes of perivascular cells and blood-brain barrier changes associated with suicide.

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

“…Microglia activation was found in prefrontal cortex, anterior cingulate cortex and hippocampus of depression subjects who committed suicide. 29,30) Interestingly, we also found that elevated pro-inflammatory cytokines were associated with increased numbers of reactive microglia cells in the brain, indicating that CRS exposure activated this brain innate immune cells during the pathogenesis of depression.…”

Visualisation of Microglia with the use of Immunohistochemical Double Staining Method for CD-68 and Iba-1 of Cerebral Tissue Samples in Cases of Brain Contusions

“…Wherein the strong expression of this protein is associated with the activated microglia and macrophages, and the low expression is generally associated with resting microglia [21][22][23].…”

“…The lisosomal protein CD68 can be used for microglial staining [21,22]. High levels of CD68 expression are associated with macrophages and activated microglia, whilst low levels of expression are associated with resting, ramified microglia [21][22][23].…”

Microglial Gene Expression Alterations in the Brains of Patients with Psychiatric Disorders

“…Microglial activation has been observed in postmortem brains from patients with psychiatric disorders, including schizophrenia [20], mood disorders [21,22], substance abuse [23], and suicidality [24]. However, detailed mechanisms of microglia involvement in the pathogeneses of psychiatric disorders have not been elucidated.…”

“…In terms of the pathophysiology of neuropsychiatric disorders, previous studies have identified human microglial cell activation based on conventional microglia-specific markers, including major histocompatibility complex, class II, DR (HLA-DR), complement receptor type3 (CD11b, also known as integrin, alpha-M; ITGAM), ionized calcium binding adaptor molecule 1 (IBA1, also known as allograft inflammatory factor 1; AIF1), macrophage antigen CD68, (CD68, also known as macrosialin), and glucose transporter type 5 (GLUT5, also known as solute carrier family 2, member 5; SLC2A5) [20,[24][25][26], in psychiatric illnesses, which are described below. Based on these observations, theories on the neuropsychoimmunological mechanisms of neuropsychiatric disorders have been proposed, including immunological alterations that have been demonstrated in peripheral blood and cerebrospinal fluid samples from patients with psychiatric illnesses.…”