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Intracerebroventricular streptozotocin induces impaired Barnes maze spatial memory and reduces astrocyte branching in the CA1 and CA3 hippocampal regions

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Sporadic Alzheimer’s disease (SAD) is the most common form of dementia; therefore, there is an urgent need for a model that recapitulates the main pathologic hallmarks of this disease. The intracerebroventricular (icv) injection of streptozotocin (icv-STZ) in rats constitutes a promising model, and thus, icv-STZ rats develop insulin-resistant brain state and cognitive impairments. Even though a great piece of studies has hitherto described this system as a model for SAD, further behavioral and morphometric studies are still needed to fully characterize it. In this study, using Sprague Dawley rats, we evaluated short-term effects on behavior and hippocampus morphometry of the icv-STZ injection at two doses: 1 (STZ1) and 3 mg/kg (STZ3). We found that, following icv-STZ injection, STZ3 animals, but not STZ1, exhibited impairments in spatial reference learning and memory (Barnes maze test) and in recognition memory (object recognition test). Furthermore, the results from behavioral and morpho-histochemical data are compatible. STZ3 rats displayed Stratum Radiatum volume reduction and a decreased NeuN immunoreactivity (neuron loss) in hippocampal CA1 region, together with an increased immunoreactivity for microglial (Iba1) and astroglial (GFAP) markers (neuroinflammation). Sholl analysis revealed the vulnerability of hippocampal astrocytes to STZ in CA1 and CA3. Thus, both doses induced a reduction in process length and in the number of main processes, accompanied by a frank decrease in branching complexity. The present study provides important knowledge of this AD rat model. Overall, we found that the only high STZ dose induced severe and acute neurodegenerative lesions, associated with an inflammation process.

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Acknowledgements

The authors thank to Dr. Joaquín Pardo, Ms. Natalia Scelcio, and Ms. Romina Becerra for technical assistance, Ms. Rosana del Cid for English edition, Mr. Mario R. Ramos for graphic designs, and Mr. Oscar Vercellini, Araceli Bigres, and Juan Manuel Lofeudo for animal care assistance. PCR and GRM are career researchers of the Argentine Research Council (CONICET). MFZV, JLH, and EFL are recipients of CONICET doctoral fellowships. LST is a recipient of National Interuniversity Council (CIN) fellowship. This work was supported by grants #PICT12-2461 and #PICT15-1998 from the Argentine Agency for the Promotion of Science and Technology and grant PIP0570 from CONICET to PCR.

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  1. Institute for Biochemical Research (INIBIOLP)-Cathedra of Histology B, School of Medical Sciences, National University of La Plata (UNLP), CC 455, Zip 1900, La Plata, Argentina

    María F. Zappa Villar, Juliette López Hanotte, Eugenia Falomir Lockhart, Lucía S. Trípodi, Gustavo R. Morel & Paula C. Reggiani

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  1. María F. Zappa Villar
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  2. Juliette López Hanotte
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Zappa Villar, M.F., López Hanotte, J., Falomir Lockhart, E. et al. Intracerebroventricular streptozotocin induces impaired Barnes maze spatial memory and reduces astrocyte branching in the CA1 and CA3 hippocampal regions. J Neural Transm 125, 1787–1803 (2018). https://doi.org/10.1007/s00702-018-1928-7

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