Transient change in GABA(A) receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration.
BACKGROUND
Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration.


RESULTS
We observed a specific reduction in gamma2 subunit gene expression, while alpha1-5, beta1-2, gamma1,3 and delta subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the gamma2 down-regulation was present only after the onset of degeneration at p14. The difference in gamma2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice.


CONCLUSIONS
In conclusion, the down-regulation of gamma2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.
Linnemann
C
C
Department of Cognitive Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Otfried-Müller-Strasse 27, 72076 Tübingen, Germany. Christoph.Linnemann@uni-tuebingen.de
Schmeh
I
I
Thier
P
P
Schwarz
C
C
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002529:Cerebellar Nuclei / Q000378:metabolism*; D003199:Computer Systems; D015536:Down-Regulation; D015870:Gene Expression; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D011689:Purkinje Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D020033:Protein Isoforms; D012333:RNA, Messenger; D011963:Receptors, GABA-A