Decline in age‐dependent, MK801‐induced injury coincides with developmental switch in parvalbumin expression: Cingulate and retrosplenial cortex

Abstract

Age-dependent, MK801-induced, activated caspase-3 expression in the postnatal brain is generally not observed in neurons expressing calcium-binding proteins (CaBPs), suggesting that apoptosis and calcium buffering are inversely related. In regions such as the cingulate and retrosplenial cortex, injury peaks at postnatal Day 7 (P7) and rapidly diminishes thereafter, whereas expression of calbindin (CB) and calretinin (CR) was relatively low from P0 to P7 and steadily increased from P7 to P14. At ages thereafter, CB and CR expression either remained stable then declined or rapidly declined. Parvalbumin (PV) was generally low-absent prior to P7 but expression dramatically increased from P10 onwards, peaking at P21. These studies suggest calcium entry (through N-methyl-D-aspartate receptor (NMDARs)) and buffering (by CaBPs) are integral to normal CNS maturation. Because schizophrenia is associated with glutamate hypo-function, developmental injury, and aberrant CaBP expression, our data indicate that this postnatal brain injury model may offer important insights into the nature of this disorder.

Decline in age‐dependent, MK801‐induced injury coincides with developmental switch in parvalbumin expression: Somatosensory and motor cortex

“…2A, B, C) or Ctx II of M1/M2 (Fig. 2D, E, F), supporting previous findings documented in the first paper in this series (Lema Tomé et al, 2007). …”

“…Additionally, CB expression was also substantially increased after P14 due to the appearance of a layer of lightly-labeled CB-positive cells in all three regions studied. At P21, when sensitivity to MK801 is absent, expression of CB and especially PV remained high, consistent with previously published work (Lema Tomé et al, 2006a; Lema Tomé et al, 2007; Turner et al, 2007a) suggesting that developmental regulation of CaBP expression may underlie susceptibility of the early neonatal brain to MK801 and other drugs that alter calcium homeostasis.…”

“…Expression of the pro-apoptotic marker was found to peak at P7, diminish at P14 and was absent at P21. These results agree with reports in other cortical areas (Ikonomidou et al, 1999; Lema Tomé et al, 2007; Turner et al, 2007b). …”

“…1H). Data from both CNS regions are consistent with previous studies from our lab that examine injury from NMDAR blockade in other parts of the brain (Lema Tomé, Miller, Bauer, Nottingham, Smith, Blackstone, Brown, Bryan, Leigh, Brady, Busch, & Turner, 2007), or using independent markers of apoptosis (Ikonomidou et al, 1999; Turner et al, 2007b). …”

Fgfr1 Inactivation in the Mouse Telencephalon Results in Impaired Maturation of Interneurons Expressing Parvalbumin

“…This postnatal maturation period coincides temporally with the periods of plasticity in the sensory cortex, and has been implicated in the establishment of critical periods for visual system development. Interestingly, experiments with NMDA receptor antagonist MK801 have also revealed this to be a time of vulnerability for PV+ interneurons [42], [43]. The KV3.1b potassium channel that confers fast spiking properties to PV+ basket cells and chandelier neurons is also upregulated in the maturing cortex during the juvenile to young adult stages [19], [20].…”