Astrocytes In Multiple Sclerosis Research Articles

Aminergic receptors in astrogliotic plaques from patients with multiple sclerosis

Cultured astrocytes express a spectrum of neurotransmitter receptors. However, little is known about these receptors in situ. We previously reported the absence of β 2 adrenergic receptors on astrocytes in multiple sclerosis (MS). Here we used [ 3H]−radioligands and receptor autoradiography to screen for a variety of other aminergic receptors in six silent chronic astrogliotic plaques in brain tissue obtained from five patients with MS. Dopamine D 1 and histamine H 1 receptors were absent. We detected specific binding for cholinergic muscarinic receptors > dopamine D 2, α 1- and α 2−adrenergic receptors > 5-HT 1A, 5-HT 1B/D, 5-HT 2A, 5-HT 2c, 5-HT 4, and dopamine D 3 receptors. Radiotracers for these aminergic receptors might be useful for studying astrogliosis in patients with MS, and compounds acting at some of these receptors may have potential to modulate astroglial function in MS.

3H]dihydroalprenolol binding to beta adrenergic receptors in multiple sclerosis brain

By using immunocytochemistry we previously reported the absence of β 2 adrenergic receptors on astrocytes in multiple sclerosis (MS) white matter. Here, we measured β 1 and β 2 adrenergic receptor concentrations in postmortem brain sections of six MS patients and six controls by using quantitative autoradiography with [ 3H]dihydroalprenolol. White matter contained no β 1 adrenergic receptors. In white matter of controls low levels of β 2 adrenergic receptors were detected. In agreement with the immunohistochemical study, we were unable to detect β 2 adrenergic receptors in both normal appearing white matter and astrogliotic plaques in MS. Concentrations of β 1 and β 2 adrenergic receptors in cerebral cortex were not different between controls and MS patients.

Expression of heat shock protein-65 by oligodendrocytes in vivo and in vitro: implications for multiple sclerosis.

We studied immunoreactivity for heat shock proteins (HSPs) in multiple sclerosis (MS) brain tissue and detected HSP-65 in chronic MS plaques at the edge of thinly myelinated (or remyelinated) areas. Serial-section immunocytochemistry and double staining revealed that HSP-65+ cells represented reactive, immature oligodendrocytes with strong reactivity for myelin basic protein and weak reactivity for galactocerebroside. Mature oligodendrocytes outside MS plaques did not stain for HSP-65. Control brain sections showed no HSP-65 reactivity. Oligodendrocytes expressed HSP-65 in mixed glial cell cultures. In this system in vitro, oligodendrocytes, but not astrocytes, showed constitutive expression of HSP-65. There was immunoreactivity for HSP-72 in astrocytes in MS and non-MS brains to a similar extent but no association between HSP-72 reactivity and MS plaques. Interestingly, HSP-65+ oligodendrocytes colocalized with T lymphocytes expressing the gamma delta T-cell receptor (TcR). Since HSP-65 has been implicated as a major antigen recognized by TcR gamma delta lymphocytes, our findings might represent a new immunologic interaction within MS plaques that leads to the destruction of immature oligodendrocytes involved in remyelination.