Primary Central Nervous System Lymphoma (PCNSL) is a rare form of extra nodal non-Hodgkin's lymphoma. HIV patients are more prone to PCNSL. It may arise from a systemic lymphoma that seeds multiple organs, including the brain. The predominant histology of PCNSL is large B-cell lymphoma. Molecular studies on systemic AIDS/NHL is well characterized, however, information on molecular studies of PCNSL is limited due in part to accessibility of tissue and lack of animal model. To date, no animal model has been developed, which recapitulates both histopathologic and molecular features of this disease, including the immune phenotypic state. We recently developed an animal model of PCNSL. The observation of a phenotype of a HIV -1 transgenic mouse model that develops a B- cell lymphoma that mimics the disease is seen in AIDS patients with NHL Brain lymphoma patients. HIV associated B-cell lymphoma patients as well as HIV infected patients suffer from cognatic impairment. Brain hippocampus region regulates cognatic behavior. Therefore, we were interested in finding the cellular and molecular changes in the hippocampus of these animals. Interestingly, we identified a significant increase of infiltrating leucocytes, T cells, B cells, and macrophages/microglial cells in the hippocampal region of those mice. Astrogliosis is also observed. Aquaporin-4 (AQP4) is the predominant water channel expressed by astrocytes. The regulation of AQP4 has been extensively investigated in various neuropathological conditions; however, the functional role of AQP4 in synaptic plasticity, learning, and memory is only beginning to be elucidated. We have explored the role of AQP4 and its influence on hippocampus and its potential relationship with synaptic plasticity of these mice. Recent in vitro and in vivo studies using AQP4-null and wild-type mice, in particular, the impairment of cognatic function observed in the hippocampus. (Szu JI and Binder DK. Front Integr Neurosci. 2016 Feb 24; 10:8). In this context we found increased AQP4 and synaptic plasticity (by detecting synaptophysin and synapsine-1) in the hippocampus of these animals. This suggests that AQP4 plays an important role in regulating synaptic plasticity in the hippocampus of these mice. Astrocytes play a role in synaptic plasticity. However, there are only a few studies that implicate a direct relationship of AQP4 in synaptic plasticity. All together, these studies highlight the potential influence of AQP4 in synaptic plasticity and memory of these animals probably due to compensatory mechanism.