Abstract: The present disclosure provides a method for treating depression using a therapeutically effective amount of a pharmaceutical agent. The pharmaceutical agent can inhibit an activity of an astroglial potassium channel, and especially inhibit the functionality of Kir4.1, in astrocytes in the lateral habenula of a subject so that the abnormal burst firings of neurons in the lateral habenula of the subject can be suppressed. The pharmaceutical agent can include a vector expressing a target nucleotide sequence in the astrocytes in the lateral habenula, whose expression is configured to suppress Kir4.1 expression by RNA interference, or to block Kir4.1 functionality by a dominant negative effect of a mutant Kir4.1 protein. The pharmaceutical agent can alternatively comprise a small molecule compound, or an active macromolecule such as an anti-Kir4.1 antibody, that can directly inhibit the astroglial potassium channel activity.

Abstract: A method for treating a subject with depression characterized by having an increased burst firing in neurons of a lateral habenula in the subject is provided. The method includes a step of administering to the subject a pharmaceutical composition capable of inhibiting the burst firing in the lateral habenula of the subject. The pharmaceutical composition includes one or more active pharmaceutical agents, which can suppress the burst firing in the lateral habenula of the subject and can include at least one of an N-methyl-D-aspartate receptor (NMDAR) inhibitor or a T-type calcium channel inhibitor. The pharmaceutical composition can be in a formulation allowing for local administration to the lateral habenula of the subject, or can be in a formulation configured for systemic administration to the subject. A method for testing a test substance for an antidepressive effect is also provided.

Abstract: In light of a discovery that astroglial Kir4.1 in lateral habenula drives neuronal bursts in depression, the present disclosure provides a pharmaceutical agent and a method of use thereof for treating depression. The pharmaceutical agent can inhibit an activity of an astroglial potassium channel, and especially suppress expression or functionality of Kir4.1, in astrocytes in the lateral habenula of a subject so that bursting activity of neurons in the lateral habenula of the subject can be suppressed. The pharmaceutical agent can include a vector expressing a target nucleotide sequence in the astrocytes in the lateral habenula, whose expression is configured to suppress Kir4.1 expression by RNA interference, or to block Kir4.1 functionality by a dominant negative effect of a mutant Kir4.1 protein. The pharmaceutical agent can alternatively comprise a small molecule compound, or an active macromolecule such as an anti-Kir4.1 antibody, configured to directly inhibit the astroglial potassium channel activity.

Abstract: In light of a discovery that astroglial Kir4.1 in lateral habenula drives neuronal bursts in depression, the present disclosure provides a pharmaceutical agent and a method of use thereof for treating depression. The pharmaceutical agent can inhibit an activity of an astroglial potassium channel, and especially suppress expression or functionality of Kir4.1, in astrocytes in the lateral habenula of a subject so that bursting activity of neurons in the lateral habenula of the subject can be suppressed. The pharmaceutical agent can include a vector expressing a target nucleotide sequence in the astrocytes in the lateral habenula, whose expression is configured to suppress Kir4.1 expression by RNA interference, or to block Kir4.1 functionality by a dominant negative effect of a mutant Kir4.1 protein. The pharmaceutical agent can alternatively comprise a small molecule compound, or an active macromolecule such as an anti-Kir4.1 antibody, configured to directly inhibit the astroglial potassium channel activity.

Abstract: A method for treating a subject with depression characterized by having an increased burst firing in neurons of a lateral habenula in the subject is provided. The method includes a step of administering to the subject a pharmaceutical composition capable of inhibiting the burst firing in the lateral habenula of the subject. The pharmaceutical composition includes one or more active pharmaceutical agents, which can suppress the burst firing in the lateral habenula of the subject and can include at least one of an N-methyl-D-aspartate receptor (NMDAR) inhibitor or a T-type calcium channel inhibitor. The pharmaceutical composition can be in a formulation allowing for local administration to the lateral habenula of the subject, or can be in a formulation configured for systemic administration to the subject. A method for testing a test substance for an antidepressive effect is also provided.