Abstract: Antagonists of group 1 metabotropic glutamate receptors (mGluR) potentiate the effect of positive AMPA receptor modulators on neurotrophin expression, such as brain-derived neurotrophic factor (BDNF). The findings described herein suggest a combinatorial approach for drug therapies, using both positive AMPA receptor modulators and mGluR antagonists, to enhance brain neurotrophism.

Abstract: Antagonists of group 1 metabotropic glutamate receptors (mGluR) potentiate the effect of positive AMPA receptor modulators on neurotrophin expression, such as brain-derived neurotrophic factor (BDNF). The findings described herein suggest a combinatorial approach for drug therapies, using both positive AMPA receptor modulators and mGluR antagonists, to enhance brain neurotrophism.

Abstract: Antagonists of group 1 metabotropic glutamate receptors (mGluR) potentiate the effect of positive AMPA receptor modulators on neurotrophin expression, such as brain-derived neurotrophic factor (BDNF). The findings described herein suggest a combinatorial approach for drug therapies, using both positive AMPA receptor modulators and mGluR antagonists. to enhance brain neurotrophism.

Abstract: The present invention provides brain cells, such as normal brain cells, apolipoprotein E deficient brain cells, or apoE4 containing brain cells, that are treated with a compound which can modulate integrins and/or integrin receptors to produce increased sequestration of and/or accumulation of and/or uptake of A?, and/or changes in cathepsin D content and/or lysosomal dysfunction, and/or microglia activation in the brain cells. The present invention also provides methods for producing such cells and methods for using the cells for screening an agent or substance that modulates the sequestration of and/or accumulation of and/or uptake of A?, and/or lysosomal dysfunction, and/or changes in cathepsin D content and/or microglia activation in the brain cells. The method further provides a new therapeutic target, antagonism of glutamate receptors, for the treatment of neurodegenerative diseases which are characterized by inter alia, abnormal amyloid uptake and/or accumulation.

Abstract: Cultured brain slices are treated with a free radical generator, in the presence of a lysosomal enzyme inhibitor (specifically an inhibitor of two cathepsins). The treated brain slices rapidly develop autofluorescent lipofuscin granules—a universal feature of brain aging. Other correlates of the aged brain are also induced by this treatment, thereby providing an in vitro model for (1) the study of brain aging; (2) assessment of anti-brain aging drugs; and (3) therapeutics directed at the clinical condition referred to as neuronal ceroidlipofuscinosis.

Abstract: The present invention provides brain cells, such as normal brain cells, apolipoprotein E deficient brain cells, or apoE4 containing brain cells, that are treated with a compound which can modulate integrins and/or integrin receptors to produce increased sequestration of and/or accumulation of and/or uptake of A&bgr;, and/or changes in cathepsin D content and/or lysosomal dysfinction, and/or microglia activation in the brain cells. The present invention also provides methods for producing such cells and methods for using the cells for screening an agent or substance that modulates the sequestration of and/or accumulation of and/or uptake of A&bgr;, and/or lysosomal dysfunction, and/or changes in cathepsin D content and/or microglia activation in the brain cells. The method further provides a new therapeutic target, antagonism of glutamate receptors, for the treatment of neurodegenerative diseases which are characterized by inter alia, abnormal amyloid uptake and/or accumulation.

Abstract: Cultured brain slices are treated with a free radical generator, in the presence of a lysosomal enzyme inhibitor (specifically an inhibitor of two cathepsins). The treated brain slices rapidly develop autofluorescent lipofuscin granules-a universal feature of brain aging. Other correlates of the aged brain are also induced by this treatment, thereby providing an in vitro model for (1) the study of brain aging; (2) assessment of anti-brain aging drugs; and (3) therapeutics directed at the clinical condition referred to as neuronal ceroid-lipofuscinosis.

Abstract: Methods for increasing the level of neurotrophic factors and neurotrophic factor receptors in the brain of a mammal afflicted with a pathology which produces neurodegeneration without significant loss of memory or learning comprising administering to a mammal an effective amount of an allosteric upmodulator of .alpha.-amino-3-hydroxy-5-methyl-isoxazole-4-proprionic acid (AMPA) receptors.

Abstract: The activation of neurons in specific areas of a mammalian brain are determined by measurement of levels of mRNA following administration of an agent that potentially affects neuronal activity. Differential levels of mRNA caused by an agent can be measured, as can the specific distribution of the alteration of neuronal activity. Many mental disorders are associated with the abnormal function of a particular area of the brain. The present invention allows the determination of which area of the brain, if any, is affected by an administered agent. Accordingly, the invention provides a valuable tool for assaying compounds as potential therapeutic agents.