Upregulation of MAP1B and MAP2 in the Rat Brain after Middle Cerebral Artery Occlusion: Effect of Age

Abstract

Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. This is especially important when studying restorative processes that are age dependent. To explore the potential of older animals to initiate regenerative processes after cerebral ischemia, the authors studied the expression of the juvenile-specific cytoskeletal protein, microtubule-associated protein (MAP) 1B, and the adult-specific protein, MAP2, in male Sprague-Dawley rats at 3 months and 20 months of age. The levels of MAP1B and MAP2 transcripts and the corresponding proteins declined with increasing age in the hippocampus. In the cortex, the levels of the transcripts did not change significantly with age, but the morphologic features of immunostained fibers were clearly affected by age; that is, cortical MAP1B fibers became thicker, and MAP2 fibers, more diffuse, in aged rats. Focal cerebral ischemia, produced by reversible occlusion of the right middle cerebral artery, resulted in a large decrease in the expression of both MAP1B and MAP2 in the infarct core at the messenger ribonucleic acid and protein levels. However, at 1 week after the stroke, there was vigorous expression of MAP1B and its messenger ribonucleic acid, as well as MAP2 protein, in the border zone adjacent to the infarct of 3-month-old and 20 month-old male Sprague-Dawley rats. The upregulation of these key cytologic elements generally was diminished in aged rats compared with young animals, although the morphologic features of fibers in the infarct border zone were similar in both age groups. These results suggest that the regenerative potential of the aged rat brain appears to be competent, although attenuated, at least with respect to MAP1B and MAP2 expression up to 20 months of age.

Cellular and Molecular Events Underlying the Dysregulated Response of the Aged Brain to Stroke: A Mini-Review

“…Growth-promoting factors include growth-associated proteins GAP43 and CAP23, the growth-promoting transcription factor c-jun, the growth-promoting cell guidance molecule L1, the CDK5-inhibitor p21, microtubule-associated proteins MAP1B and MAP2, immature neurons marker doublecortin, and stem cell marker nestin [26,[29][30][31] . Pathogenesis of tissue damage is mainly due to inflammatory interactions involving cytokines, chemokines and leukocytes and neurotoxic factors like the C-terminal fragment of ␤ -amyloid (A ␤ ) [11,23,26,[32][33][34] .…”

“…Interestingly, the number of degenerating neurons did not rise further in aged animals, even though the infarcted area continued to expand, so that by day 7 the numbers of degenerating neurons were almost the same in both age groups ( fig. 3 C) [23,29] .…”

“…6 A) and, to a lesser extent, 20-month-old rats ( fig. 6 B) at 14 days following the stroke [26,29] . Similarly, MAP2 protein and mRNA were upregulated in the periinfarcted area at almost the same levels both in young ( fig.…”

Brain Plasticity and Stroke Rehabilitation

“…In a comparison between 3-and 20-month-old rats, upregulation of MAP1B and MAP2 was diminished but not abolished in the aged compared with the young animals. 147 It might not be fair to compare humans with rats living their entire lives in a laboratory with little stimulation. The decrease in synaptic density in aged laboratory rats can be prevented by rearing in an enriched environment.…”

Neuroplasticidade induzida pelo exercício: efeitos sobre o hipocampo e regiões motoras do encéfalo de ratos.

“…Pode-se observar uma redução de MAP2 após a oclusão reversível da artéria cerebral média seguida de um aumento 1 semana após a reperfusão (Popa-Wagner et al, 1999). Já foi observado que a idade avançada reduz a imunorreatividade para MAP2 (Di Stefano et al, 2006;Himeda et al, 2005).…”