Differential regulation of astrocytic mRNAs in the rat striatum after lesions of the cortex or substantia nigra.

This study evaluates the time course of expression of three astrocytic mRNAs, glial fibrillary acidic protein (GFAP), apolipoprotein E (ApoE), and clusterin, in the rat striatum (ST) following a unilateral lesion of either the cortex (CX) or the substantia nigra (SN), using Northern blot and in situ hybridization analyses. We found that while there was a time-dependent increase in astrocytic GFAP mRNA in the deafferented ST following both the CX and the SN lesions, the time course of the response was different between the two lesion paradigms. Specifically, the increase in GFAP mRNA in striatal astrocytes after the SN lesion was rapid and transient returning to control levels by 10 days postlesion, while the response was long lasting and remained increased until at least 27 days after the CX lesion. In addition, the mRNA response for both ApoE and clusterin was differentially regulated in response to the two lesions. Specifically, both clusterin and ApoE mRNAs were rapidly increased in the ST following the CX lesion while both mRNAs remained unchanged following the SN lesion. Data from this study extend information derived from previous investigations on the multifunctional role of astrocytes in the response to brain injury. Specifically, our data support the notion that while the time course of the GFAP response in striatal astrocytes may vary between lesion paradigms, the upregulation of GFAP is part of a generalized response of reactive astrocytes to diverse brain injuries. By comparison, upregulation of the mRNAs for the lipoproteins clusterin and ApoE are lesion specific and may play a role in the transport of recycled myelin lipids from dying axons to actively growing axons and dendrites in reactive synaptogenesis.