Correlated inflammatory responses and neurodegeneration in peptide-injected animal models of Alzheimer's disease

Abstract

Animal models of Alzheimer's disease (AD) which emphasize activation of microglia may have particular utility in correlating proinflammatory activity with neurodegeneration. This paper reviews injection of amyloid- β (A β ) into rat brain as an alternative AD animal model to the use of transgenic animals. In particular, intrahippocampal injection of Aβ 1-42 peptide demonstrates prominent microglial mobilization and activation accompanied by a significant loss of granule cell neurons. Furthermore, pharmacological inhibition of inflammatory reactivity is demonstrated by a broad spectrum of drugs with a common endpoint in conferring neuroprotection in peptide-injected animals. Peptide-injection models provide a focus on glial cell responses to direct peptide injection in rat brain and offer advantages in the study of the mechanisms underlying neuroinflammation in AD brain.

Figure 1

Glial responses in AD animal model. (a) Representative microgliosis (Iba-1 marker) for controls (PBS and reverse peptide Aβ _42-1, respective left and middle panels) and Aβ _1-42 (right panel). (b) Typical astrogliosis (GFAP marker) for the same animal groups as in (a).

Figure 2

Viability of GCL neurons in animal model. Representative neuronal expression (NeuN marker) for the same animal groups as in Figure 1. Left and middle panels show NeuN for respective PBS and reverse peptide controls. Right panel is marker staining for Aβ _1-42 injection.

Figure 3

Microglial and neuronal responses in angiostatin-treated rats. (a) Representative microgliosis is shown for Aβ _1-42-injected animals (left panel) and for peptide-injected animals receiving angiostatin treatment (right panel). (b) Typical expression of GCL neurons for untreated peptide-injected (left panel) and angiostatin-treated (right panel) animals.