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. 2011 Mar;232(1-2):8-16.
doi: 10.1016/j.jneuroim.2010.09.009. Epub 2010 Oct 14.

Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair

Zhongqi-Phyllis Wu  1 , Lorraine Washburn, Tina V Bilousova, Maia Boudzinskaia, Nathalie Escande-Beillard, Jyes Querubin, Hoa Dang, Cui-Wei Xie, Jide Tian, Daniel L Kaufman
Affiliations

Enhanced neuronal expression of major histocompatibility complex class I leads to aberrations in neurodevelopment and neurorepair

Zhongqi-Phyllis Wu et al. J Neuroimmunol. 2011 Mar.

Abstract

Mice deficient in classical major histocompatibility complex class I (MHCI) have aberrations in neurodevelopment. The consequences of upregulated neuronal MHCI expression have not been examined. We found that transgenic C57Bl/6 mice that are engineered to express higher levels of self-D(b) on their CNS neurons have alterations in their hippocampal morphology and retinogeniculate projections, as well as impaired neurorepair responses. Thus, enhanced neuronal classical MHCI expression can lead to aberrations in neural circuitry and neurorepair. These findings complement a growing body of knowledge concerning the neurobiological activities of MHCI and may have potential clinical relevance.

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Conflict of interest statement

All authors declare that there are no conflicts of interest

Figures

Fig. 1
Fig. 1. Anterograde tracing of RGC afferents and quantitation of projection areas in the dLGN
Representative images of ipsilateral (A, C) and contralateral (B, D) projections in wildtype and NSE-Db mice. Scale bar=0.067 mm. Quantification of ipsilateral (E), and contralateral projections (F), as well as total dLGN (G) areas in wildtype (open bars) and NSEDb (black bars) mice. H) Ipsilateral/dLGN area ratio. Data shown are mean+/−SEM. N = 13 wildtype, 15 NSE-Db mice. *=p<0.05, ***=p<0.005.
Fig. 2
Fig. 2. Normal basal synaptic transmission and LTP in the hippocampal CA1 region of NSE-Db mice
(A) The synaptic input-output relationship at Schaffer collateral-CA1 synapses of wildtype (open squares) and NSE-Db mice (black diamonds). (B) Induction of early LTP by a single HFS in wildtype (open squares) and NSE-Db mouse hippocampus (black diamonds). For both A and B, N=1 slice per animal, 8–12 animals/group.
Fig. 3
Fig. 3. Reduced synaptophysin and GAP-43 immunostaining in the hippocampal regions of NSE-Db mice
(A) Representative images of anti-synaptophysin staining in the dentate gyrus (DG), CA3 and CA1 regions of wildtype (WT) and NSE-Db mice. Black boxes show sampling areas for each region. (B) Densitometric group data of synaptophysin immunoreactivity in hippocampal regions of wildtype and NSE-Db mice. Black bars=wildtype, open bars=NSE-Db mice. Data shown is mean ± SEM. (C) Representative images of anti-GAP-43 staining in different hippocampal regions of wildtype and NSE-Db mice. (D) Densitometric group data of GAP-43 immunoreactivity in hippocampal regions of wildtype and NSE-Db mice. N=8 slices/mouse, 8 mice/group. *=P<0.05, **=P<0.01, ***=P<0.001 by Student’s t-test. Scale bar=100 µm.
Fig. 4
Fig. 4. NSE-Db mice display reduced number of pyramidal neurons in the CA1 hippocampal region
(A) Representative images of NeuN/DAPI stained cells in the CA1, CA3 and DG of the hippocampus. White boxes are representative counting frames for each region. Scale bar=100 µm. (B) Layer width, (C) cell number, and (D) cells per unit length in hippocampal regions of NSE-Db mice were calculated as described in Methods. N=6 sections from at least 5 animals/group. *=P<0.05, **=P<0.01 by Student’s t-test.
Fig. 5
Fig. 5. NSE-Db mice have deficiencies in compensatory sprouting responses after hippocampal lesioning
The perforant path of wildtype (wt) C57BL/6 or NSE-Db mice was unilaterally lesioned. After 14 days, coronal brain sections were stained for AChE. Representative AChE stained sections from lesioned wt (A) and NSE-Db mice (B). The AChE staining patterns on unlesioned side of wt and NSE-Db mice were similar. On the lesioned side, compensatory cholinergic sprouting responses occurred in the molecular layer (ML) of wt, but not NSE-Db mice. (C) Group data of the mean ratio (lesioned/unlesioned) AChE staining density in the ML of wt and NSE-Db mice ± SEM. **=p<0.001. (N=6–8 mice/group). (D) Wt (□) and NSE-Db (●) mice showed similar ability to perform a hippocampal-dependent spatial task preoperatively and similar deficits immediately following lesioning. By 12–14 days post-lesion wt mice recovered their ability to perform the task, while NSE-Db mice displayed recovery deficits. Data shown is mean percent alternation ± SEM (*=p<0.05). (N=15 mice/group).
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References

    1. Bai A, Broen J, Forman J. The pathway for processing leader-derived peptides that regulate the maturation and expression of Qa-1b. Immunity. 1998;9:413–421. - PubMed
    1. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004;16:1–13. - PubMed
    1. Banks WA, Kastin AJ, Broadwell RD. Passage of cytokines across the blood-brain barrier. Neuroimmunomodulation. 1995;2:241–248. - PubMed
    1. Barco A, Alarcon JM, Kandel ER. Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell. 2002;108:689–703. - PubMed
    1. Bauer A, Huttinger R, Staffler G, Hansmann C, Schmidt W, Majdic O, Knapp W, Stockinger H. Analysis of the requirement for beta 2-microglobulin for expression and formation of human CD1 antigens. Eur J Immunol. 1997;27:1366–1373. - PubMed

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