Short term recognition memory can be measured using the novel object recognition (NOR) task. In one embodiment, the method comprises a behavioral test score, which can be measured by administering the molecule to a mammal and grading the mammal's behavioral performance. The calcium oscillation assay and/or the sequence score method can be especially useful for screening numerous candidate molecules to determine their in vivo neurotoxicities. For example, long term toxicities can be determined by measuring the change in tubulin intensity in a cell by the molecule when the cell comes in contact with a molecule. Examples of assays measuring the change in tubulin intensity in a cell are provided below. In certain embodiments, the change in tubulin intensity is measured along with one or both of the change in calcium oscillation, sequence score, and/or in vivo tolerability assay. In some embodiments, the tubulin intensity in a cell that is not exposed to the tested molecule is referred to as the tubulin intensity in a control cell.



In some embodiments, the molecule exhibits tubulin intensity in a cell greater than or equal to 99%, greater than or equal to 98%, greater than or equal to 97%, greater than or equal to 96%, greater than or equal to 95%, cams online sex greater than or equal to 90%, greater than or equal to 85%, greater than or equal to 80%, greater than or equal to 75%, or greater than or equal to 70% of tubulin intensity in a cell that is not exposed to the molecule, i.e., a control cell, as defined above. In some embodiments, the molecule reduces less than about 30%, less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, or less than about 1% of the tubulin intensity in a vehicle control cell. In certain embodiments, the methods of the disclosure further comprise measuring long term in vivo toxicities of a molecule. The disclosure also provides a method of administering a molecule to a subject for the treatment of a neurological disease or condition.





In other embodiments, the disclosure includes a method of identifying or selecting a molecule having tolerable in vivo neurotoxicity comprising (i) performing a calcium oscillation assay, (ii) calculating sequence score, (iii) performing an in vivo tolerability study, and (iv) administering the molecule to a mammal in need of treatment of a disease or condition. In some embodiments, the disclosure provides a method of treating a mammal, e.g., a human, comprising (1) selecting a molecule having tolerable in vivo acute neurotoxicity as described elsewhere herein (e.g., calcium oscillation assay, sequence score calculation, and/or in vivo tolerability study) and (2) administering the molecule to the mammal. In still other embodiments, the method comprising a calcium oscillation assay, a sequence score method, and/or in vivo tolerability test can further comprise administering the selected molecule to a subject in need thereof. When used in combination, if the molecule is selected as a molecule with acceptable neurotoxicity for more than one method, then the molecule is considered to have a greater chance of having acceptable neurotoxicity when administered to a test subject or patient. Therefore, for therapeutics, an animal or a human, suspected of having a disease or disorder can be treated by administering molecules in accordance with this disclosure.



The in vivo tolerability study can also be used after selecting a small number of candidate molecules after performing the calcium oscillation assay and/or sequence score calculation. In other embodiments, the present invention is also directed to a method of selecting or identifying a molecule having tolerable in vivo neurotoxicity by performing in vivo tolerability studies. In certain embodiments, the invention provides a method for both selecting a molecule and then utilizing the molecule. In other embodiments, an in vivo tolerability study can be used in combination with the calcium oscillation assay and/or the sequence score method. The laboratory animal can be a mammal, e.g., a rodent, such as a mouse, rat, guinea pig or hamster, but can also be another animal typically used in laboratory testing. Censors have closed down many services in recent years, but in a constant game of cat and mouse, providers and users have found other ways to share adult content, whether it’s self-made or pirated from the likes of Japan’s 1pondo Studio.



The laboratory animal can be a rodent, such as a mouse, rat, guinea pig or hamster, but can also be another animal typically used in laboratory testing. NOR testing is based on the spontaneous behavior of rodents to explore a novel object more than a familiar one (Dodart et. In one embodiment, a behavioral score is obtained with a novel object recognition test. In some embodiments, the behavioral score is measured by the following methods, including a novel object rejection test, a water maze test, a gait analysis test, and/or Camsonlinesex.com any combination thereof. In certain embodiments, the behavioral test is a short term memory test, a spatial learning and memory test, Camsonlinesex.com a gait analysis test, or any combination thereof. In another embodiment, a spatial learning and memory test can be assessed by a modified Morris Water Maze test as necessary. Spatial learning and memory can be assessed based on a Morris Water Maze test as shown in Morris J. Neurosci. The gait analysis test can be measured by the Catwalk assay shown in Example 5 or a modified Catwalk test as necessary.